Drospirenone has the chemical formula (2′S,6R,7R,8R,9S,10R,13S,14S,15S,16S)-1,3′,4′,6,7,8,9,10,11,12,13,14,15,16,20,21-hexadecahydro-10,13-dimethylspiro[17H-dicyclopropa[6,7:15,16]cyclopenta[α]phenanthrene-17,2′(5′H)-furan]-3,5′(2H)-dione. Drospirenone is a synthetic progestational compound having a molecular weight of 366.49 and a molecular formula of C24H30O3. Ethinyl estradiol has the chemical formula (17α)-19-norpregna-1,3,5(10)-trien-20-yne-3,17-diol. Ethinyl estradiol is a synthetic estrogenic compound having a molecular weight of 296.4 and a molecular formula of C20H24O2.
YASMIN® 28 Tablets is an oral contraceptive regimen consisting of 21 active film-coated tablets, each containing 3.0 mg of drospirenone and 0.030 mg of ethinyl estradiol, and 7 inert film-coated tablets. The inactive ingredients are lactose monohydrate NF, corn starch NF, modified starch NF, povidone 25000 USP, magnesium stearate NF, hydroxypropylmethyl cellulose USP, macrogol 6000 NF, talc USP, titanium dioxide USP, ferric oxide pigment, and yellow NF. The inert film-coated tablets contain lactose monohydrate NF, corn starch NF, povidone 25000 USP, magnesium stearate NF, hydroxypropylmethyl cellulose USP, talc USP, and titanium dioxide USP.
U.S. Pat. No. 5,976,570 describes a process for making a pharmaceutical composition comprising the steps of: (i) preparing an aqueous medium comprising one or more pharmaceutically acceptable surfactants, wherein the quantity of said surfactant or surfactants is sufficient to support a medicinal agent in solution; and (ii) granulating said one or more low dosage medicinal agents in said aqueous medium to form a granulation.
U.S. Pat. No. 6,787,531 describes a pharmaceutical composition comprising from about 2 mg to about 4 mg of micronized drospirenone particles, about 0.01 mg to about 0.05 mg of 17α-ethinyl estradiol, and one or more pharmaceutically acceptable carriers. Micronized is defined as a surface area of greater than 10,000 cm2/g, and the following particle size distribution as determined under a microscope: not more than 2% of the particles in a given batch have a diameter of more than 30 μm, and preferably less than or equal to 20% of the particles have a diameter of greater than or equal to 10 μm and less than or equal to 30 μm, in a pharmaceutical composition.
It would be desirable to prepare a pharmaceutical composition containing drospirenone which does not require micronization of the drospirenone particles in order to achieve rapid dissolution of the drospirenone from the composition.